Action Points

Explain to interested patients that traditional subcutaneous immunotherapy can take months.

Note that this small study shows an investigational vaccine produces an equivalent immunological response after four injections over three weeks.

Point out that the vaccine is not approved for clinical use.

This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.

DALLAS, Nov. 14 -- A four-injection course of an investigational ragweed vaccine, which would collapse months of immunotherapy into three weeks, was safe and immunologic in a small study, a researcher said here.

The course of subcutaneous immunotherapy with Pollinex Quattro Ragweed produced responses similar to those seen with traditional specific immunotherapy, according to William Howland, III, M.D., medical director of Lovelace Scientific Resources in Austin, Tex.

At the same time, most of the adverse events seen in the 68-patient study were injection site reactions not deemed to be serious, reported Dr. Howland at the American College of Allergy, Asthma, and Immunology meeting here.

But studies of the ragweed vaccine have been suspended by the FDA since July, when a case of transverse myelitis was reported in a volunteer in a different clinical trial.

The British company developing the vaccine -- Allergy Therapeutics -- does not think the event is related to the medication, Dr. Howland said. His report came 11 days after company officials had what they called a "constructive" meeting with the FDA to discuss the clinical hold.

Two Pollinex Quattro vaccines used in Europe contain mixtures of grass allergens and tree allergens, but not ragweed, because that plant is not a major problem in Europe, he said.

The ragweed vaccine under development here contains an allergoid, a modified allergen that reduces the allergenicity and the risk of anaphylaxis, he said.

It's coupled with an L-tyrosine adsorbate that creates a depot effect and reduces the number of injections needed. Finally, the vaccine contains monophosphoryl lipid A (MPL), which acts as an adjuvant and causes a "TH-1-like response to the allergoid," Dr. Howland said.

Dr. Howland reported on a dose-finding study, in which volunteers were randomized to three active arms -- low dose, intermediate dose, or therapeutic dose -- or placebo.

Volunteers in the low-dose group got four injections over three weeks of 300 standardized units. Those in the intermediate-dose group got one injection of 300 units, followed by two of 700, and a final shot of 2,000 units. The therapeutic dose consisted of 300 units, followed by 700, 2,000 and 6,000 units. A total of 68 participants entered the study, 20 in each active group, and eight placebo controls.

The primary endpoint of the study was change in ragweed-specific IgG, IgG1, IgG4, and IgE from baseline to two weeks post-treatment, compared to placebo, Dr. Howland said.

In the case of the immunoglobulins, there was a "nice dose response" in all three cases, Dr. Howland said.

For IgG, for instance, the therapeutic dose led to 1,000 ng/mL of serum, on average, which was significantly better than placebo at P<0.001 and better than the low dose at P<0.05.

Levels after the intermediate dose and the low dose reached approximately 600 and 400 ng/mL, respectively, which were also significantly greater than placebo at P<0.05, he said.

While IgE levels were significantly different from placebo (at P<0.05), there was no apparent pattern based on dose, Dr. Howland said.

The researchers recorded adverse effects in 31 of the 68 patients, he said, including 12 events in the therapeutic group, eight in the intermediate-dose group, nine in the low-dose group, and two in the placebo group.

Most of the events were injection site reactions, although the researchers recorded one case of tachycardia and one of nausea, both in the therapeutic group.

Dr. Howland said the study did not look at how well volunteers were protected against allergic responses during the subsequent ragweed season.

The study shows a "pretty rapid increase in protective antibodies," said Todd Mahr, M.D., of Gundersen Lutheran Clinic in La Crosse, Wis., who was not involved in the study and is a member of the program committee for the meeting.

"That might be something that -- as it goes on -- might be available to us to offer to our patients," he said, although he cautioned it is not yet approved for use.

The study was supported by Allergy Therapeutics, which is developing the vaccine. Dr. Howland did not report any potential conflicts.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine